Acid-Base Balance Flashcards
what is whole body pH governed by?
intracellular pH levels
what is normal plasma [H]?
40 nM
what is the main challenge of acid/base regulation in the body?
[H] must be kept very low, but it is produced at extremely high levels
what is the Henderson-Hasselbalch equation?
pH = pKa + log10[A-]/[HA]
undissociated (weak) acids can buffer strong bases, and their conjugate anions can buffer strong acids
ok
what is the effective range for a base?
+/- 1 pH from the pKa
what system is most responsible for the buffering capabilities of our body? why?
the Co2- bicarbonate system is responsible for 60% of our buffering capacity
even though carbonic acid’s pKa is ~2, it is more likely to dissociate into H2O and CO2. This means the rxn can be written as
CO2 + H2O H + HCO3
w/ its own equilibrium constant and pKa of 6.1
the CO2-bicarb buffering system has a pKa of 6.1 yet still acts as an effective buffer in our body. how?
the buffer exists in an open system where CO2 is free to leave, and the buffering power is proporitonal to [HCO3], which increases as pH increases
respiratory buffering
the lungs may eliminate (during acidosis) or retain (during alkalosis CO2 to assist the CO2/HCO3 buffering system
pCO2 remains constant
respiratory compensation
lungs change pCO2 via hyper or hypoventilation in an attempt to normalize blood pH
isohydric principle
all buffersin a compartment are in equilibrium w/ each other
this allows you to measure the status of 1 buffer and infer information about the others
HCO3 buffers both the ICF and ECF equally, but they contain different amounts of HCO3. how is this possible?
the ICF is twice as big as the ECF, but it has twice as much HCO3, meaning that they are effectively buffered equivalently.
where is phosphate an important buffer?
intracellularly
what is the important buffer in muscle?
creatine phosphate
describe bones as buffers
they will accept a H in exchange for K or Na. they contain HCO3 and CO3, as well as some crystalline alkaline salts. thus, they manage acidosis.
prolonged acidosis results in bone breakdown
describe urinary buffers
phosphate is important in the urine since HCO3 is completely reabsorbed. NH3/NH4 is also important
creatinine, citrate, urate
describe some metabolic processes that generate acids or bases
- the primary producer of acid is the metabolism of carbohydrates, fat, and amino acids to produce acidic CO2
carbs- lactic acid and CO2 (acidic)
fat- ketoacids and CO2 (acidic)
organic anions (basic)
amino acids- varys. breakdown of carboxyl (basic) neutralized by the breakdown of the amine (acidic). dibasic AAs produce acids and dicarboxylic AAs produce bases. these generally cancel, but sulfer AAs mean that amino acids are net acidic
organic phosphates- acidic
nucleic acids- acidic
divalent cations (basic) can often get caught in the gut, meaning that net intake becomes acidic
OVERALL- DIET RELATED BREAKDOWN IS ACIDIC
what are the limits on urine pH?
no lower than 4.5 and no higher than 8.5
how is bicarb reabsorbed in the proximal tubule?
80% of filtered bicarb is reabsorbed via two mechanisms
- Na/H exchange pumps H into the lumen, where it combines w/ bicarb to form carbonic acid, which is converted by carbonic anhydrase to H2O and CO2 which can passively cross the membrane, where it is reconverted by carbonic anhydrase to carbonic acid, which dissociates, and the bicarb leaves the cell via Na/3bicarb cotransporter
- everything is the same, but the initial H is pumped into the lumen using an ATPase
how is bicarb reabsorbed in the ascending LOH?
using a Na/H exchange, but there is no luminal carbonic anhydrase. this reabsorbs 10-15%
how is bicarb reabsorbed in the collecting duct?
the remaining 5-10% is reabsorbed by a-intercalated cells via 2 mechanisms
- only H pump- electrogenic
- H/K exchanger- neutral
both support conversion to CO2 and diffusion through the membrane, where CA converts it back into bicarb
it leaves the basal membrane through a HCO3/Cl exchanger
how does the kidney deal with excess bicarb?
- reduced reabsorption by the proximal tubule b/c the HCO3 exceeds the Tm.
- b-intercalated cells. mirror image of the a-intercalated cell, w/ an apical bicarb/Cl exchange and a basal H pump
how is the daily acid load excreted?
most acid is removed via NH4.
this removes acids from the body because normally, NH4 is converted in the liver to urea and H, thus creating more acid. By removing the NH4, an acidic precursor is removed.
there is also a small amount of acid removed via titratable acids
how does the body get NH4 from the liver to the kidneys if it is toxic in the blood?
the liver converts two NH4s to glutamine. glutamine is then converted back to two NH4s and a-ketoglutarate in the proximal tubule
what is meant by “new bicarbonate”
when glutamine is broken down in the kidney, it creates 2 NH4s and an a-ketoglutarate. catabolism of the a-ketoglutarate generates 2 new bicarbs
how does NH4 enter the lumen after conversion from glutamine?
there are 2 mechanisms:
- the NH4 can hijack the Na/H luminal exchange, where NH4 takes the place of H.
- the NH4 dissociates into the NH3 and H inside the cell, where NH3 can diffuse across the membrane
how does the concentration of NH4 change in the descending LOH?
as water leaves the descending LOH, it concentrates the bicarb, and this favors the conversion of NH4 to NH3. some NH3 diffuses into the interstitium
how does the concentration of NH4 change in ascending LOH?
almost all secreted NH4 is reabsorbed in the ascending loop via 3 mechanisms:
- it is impermeable to NH3 diffusion, but is reabsorbed via Na/K/2Cl transporters. in this instance, the NH4 substitutes for the K.
- paracellular diffusion
- apical K channels (hijacked)
describe final NH4 excretion in the collecting duct
the NH3 and NH4 exist in equilibrium in the interstium and the ratio is determined by the pH. as bicarb is reabsorbed in the collecting duct, it shifts the ratio towards NH3, which can diffuse into the collecting duct. it combines here with NH4, which then cannot diffuse out, leaving it trapped.
in the medulla, NH4 is actively taken up into cells. when it is converted into NH3, this pushes the diffusion towards the lumen (low NH3) where it becomes trapped.
what is the main determinant of the activity of acid-base transporters in the kidney? how is this regulated?
intracellular pH- causes an increase in H transporters
this occurs via two mechanisms:
- fast- allosteric regulation/post-synthetic modifications. this occurs quickly and makes existing transporters more efficient. useful in responding to lactic acid (quick onset, quick ablation)
- slow- occurs over the course of days, changes the ratio of a to b-intercalated cells. good for responding to ketoacidosis in starvation, which occurs over days.
additionally, hepatic glutamine synthesis as well as the enzymes responsible for uptake and conversion in the PT are under transcriptional regulation via intracellular pH.
how are sodium and acid-base balance coupled in the PT?
directly via the Na/H exchanger. thus, the hormones/drugs that affect the Na/H exchanger (angiotensin II) while also have an effect on acid-base
how are sodium and acid-base balance coupled in the CD?
indirectly b/c Na and H channels exist on different cells but still effect one another.
- Na is absorbed through principal cells, creating a negative lumen that favors H secretion via a-intercalated cells
- Na reabsorption in the principal cells is accompanied by K secretion. This K feeds a K/H exchanger on the a cells
- aldosterone upregulates H-ATPase on a-cells,
describe how K balance effects acid-base regulation in the body
during K depletion (K leaving cells), this is accompanied by H loading into cells, causing cellular acidification. the kidney responds to internal cell pH, so this causes increases in H secretion and NH4 section and NH4 is also more able to out compete a dwindling number of K for kidney transporters
the opposite is true for K loading, which creates internal alkalosis and acid retention
describe the signs of metabolic acidosis
ventialtion increases cerebral blood flow increases systemic arterial dilation- warm, flushed skin decreased CO decreased GFR decreased uring pH bone fractures venoconstriction
can also lead to hypercholermia and hypokalemia
describe the signs of metabolic alkalosis
ventilation decreases CO arrhythmias cerebral blood flow decreases siezures cramps, tetany in skeletal muscle decreased GFR hyperkalemia polyuria
pCO2 and HCO3 are regulated independently by the lungs and kidneys respectively
ok
which is faster, metabolic or respiratory compensation?
respiratory begins almost instantly and is complete in hours
metabolic takes days
how is the buffering system for resipratory acidosis different than metabolic acidosis
metabolic acidosis is buffered by the CO2-bicarb buffer, and is alleviated by the generation of H2O and CO2. However, in respiratory acidosis, retention of CO2 is the problem, b/c there is too much and it is generating H2CO3
in metabolic alkalosis, we need excess CO2 to convert base into HCO3 (via OH + CO2 = HCO3). however, in respiratory alkalosis, we don’t have enough CO2 to convert into HCO3, so we need to use a different buffer.
what is the limiting factor in the respiratory compensatory response to acidosis?
the work necessary for the level of hyperventilation. bottom limit is approximately 8-10 mmHg
what is the PAG?
the anion gap-
Na- Cl - HCO3
anything more than 8-12 indicates metabolic acidosis
renal tubular acidosis
acidosis caused by renal defect in H ion secretion
dilution acidosis
volume expansion w/ normal saline causes dilution of HCO3 but doesnt effect pCO2, therefore resulting in acidosis
what is the limiting factor in the respiratory compensatory response to alkalosis?
hypoventilation-mediated hypoxia
how does the body traditionally deal with metabolic alkalosis?
the Tm of reabsorption for bicarb in the PT is not much above normal levels, so it is wasted. also, alkalosis causes suppression of bicarb uptake in other parts of the nephron and increased secretion by B cells
describe how vomiting induces alkalosis and depletions of Na and K
vomiting causes the loss of acid ie alkalosis. this effects the kidneys are the seek to reabsorb less bicarb. however, bicarb is linked to Na in the PT (via Na/bicarb cotransport) and the CD (Na absorption in PCs causes a-intercalated cells to increase H secretion, which causes HCO3 reabsorption as CO2 by these same cells). this causes a net loss of Na.
the loss of Na will cause fluid to be retained in the lumen and cause a faster flow w/ more Na, leading to lost K as well. neither of these are replaced b/c of an upset stomach.
continuous vomiting results in volume loss and RAAS activation. AGII results in upregulation of Na/H exchangers and thus bicarb retention in the PT. Similarly, aldo stimulates Na absorption, which results in increased H secretion and bicarb retention. it also enhances K secretion, aggravating hypokalemia. the hypokalemia results in intracellular acidosis, and they respond by increased NH4 secretion and increase bicarb reabsorption.
all of this results in metabolic alkalosis
contraction alkalosis
loss of fluids not containing bicarb w/ no change in pCO2 results in alkalosis
what is the only cause of respiratory alkalosis
hyperventilation
describe the UAG
same idea as the PAG
Na + K - Cl
the resulting gap is usually attributable to NH4. in healthy people, the UAG is 0 or positive. in metabolic acidosis it is negative.
